Title: Integrated Training in Neurocircuitry of Affective Disorders The proposed revised Institutional National Research Service Award Training Program will provide basic and clinical neuroscientists with the skills and mentor-guided experiences to propel them into an interdisciplinary research career designed to further the understanding of brain circuitry and affect. We request funds for two positions in Year 1 and four positions each subsequent year. The area of brain circuitry as applied to understanding psychopathology is a rapidly growing domain with great potential to inform the understanding of the causal pathways and mechanisms of affective mental illness. The Center for Neuromodulation in Depression and Stress (CNDS), in collaboration with multiple University of Pennsylvania (PENN) departments, centers and institutes is well poised to launch this novel post-doctoral fellowship based on established innovations in imaging, as well as the range of related expertise offered by the proposed multidisciplinary mentor group. The proposed training recognizes that the tools necessary to understand brain circuitry pathology require training across psychopathology, human neuroimaging methodology, statistics, engineering, neuroscience, genetics and basic translational models with associated imaging, such as optogenetics. The program will be guided by Dr. Yvette Sheline, (neuroimaging of depression and stress). Dr. John Detre (clinical neuroscience and methods development in functional neuroimaging) will be Associate Director. They are joined by numerous investigators at PENN with a rich track record of experience in imaging of affective disorders, including a cadre of investigators at the forefront of new methods development; many of these labs will be co-located, along with trainees, in a new facility. Research taking a brain circuit approach to psychopathology using a neuroscience model is a novel approach for training. The program mentors provide a unique multidisciplinary training environment in which to pursue this exciting new approach, given the established collaborations between neuroimaging researchers in the clinical and basic departments of the Perelman School of Medicine and their interface with the Biomedical Graduate Studies program. The University's role at the forefront of neuroimaging and translational neuroscience offers an opportunity to help train the next generation of young scientists who can pursue fundamental questions about abnormalities in brain circuitry in affective illness from the perspective of core psychological, neural and translational mechanisms that can inform and span traditional boundaries of psychopathology and lead to more effective treatments and identification of new targets for prevention.